This is a competing renewal for a Sexually Transmitted Infections Cooperative Research Center (STI ORG). The Southeastern STI ORG is comprised of six projects Including studies on the sexually transmitted pathogens Neisseria gonorrhoeae and Haemophilus ducreyi. Five synergistic projects explore molecular pathogenesis, immunobiology and possible vaccines for gonorrhea, and the sixth project focuses on development of a promising vaccine for H. ducreyi. The six projects are supported by an Administrative Core, a Microbiology Core and an Immunology Core. Project 1 uses the murine model of gonococcal infection to study mucosal vaccine candidates. Project 2 focuses on iron-regulated adherence factors of N. gonorrhoeae. Project 3 deals with genetic mechanisms of gonococcal resistance to mediators of innate immunity. Project 4 aims at preventing gonococcal infection by targeting the adherence factor PilG. Project 5 centers on innate host immune responses to gonococcal infection. Project 6 focuses on the H. ducreyi outer membrane protein DsrA as a chancroid vaccine using a swine model of infection. The Microbiology Core will conduct experimental human gonococcal infection experiments in support of Projects 2-5. The Immunology Core provides expertise In mucosal adjuvants and immunization protocols for gonococcal studies in mice and chancroid studies in pigs and sophisticated immune monitoring using specimens from animals and humans. The overall theme uniting these projects and cores is New Approaches to STI Prevention.